High-throughput RNA-sequencing-based transcriptomic profiles of embryonic lens development for cataract gene discovery

We applied previously established in silico whole-embryo body (WB)-subtraction-based approach to identify “lens-enriched” genes. These new RNA-seq datasets on embryonic stages E10.5, E12.5, E14.5 and E16.5 confirmed high expression of established cataract-linked genes and identified several new potential regulators in the lens. Finally, we present lens stage-specific UCSC Genome Brower annotation-tracks; these are publicly accessible through iSyTE (https://research.bioinformatics.udel.edu/iSyTE/) and enable a user-friendly visualization of lens gene expression/enrichment to help prioritize genes from high-throughput data from cataract cases. Overall design: RNA-sequencing datasets of microdissected embyonic eye lens samples from stages embryonic day E10.5, E12.5, E14.5 and E16.5 were generated. To estimate lens enriched genes we generated control “whole-embryo body (WB)” datasets. The lens enriched genes were used for enrichment level based clustering to identify gene clusters exhibiting distinct lens enrichment patterns across E10.5 to E16.5 developmental window. This new lens RNA-seq data and its accessibility through iSyTE 2.0 serves as a new integrative resource for prioritization of lens defects and/or cataract-linked candidate genes identified by other high-throughput analyses such as exome-seq and GWAS.

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Anand D, Kakrana A, Siddam AD, Huang H, Saadi I, Lachke SA